Grant: New Investigator Salary Award - PA: Inflammatory Bowel Disease

The lining of the intestine is a layer of specialized cells that forms a selective barrier to the contents of the gut. When this layer is healthy, nutrients and water can cross, but toxins and bacteria cannot. When this layer is unhealthy, the result is inflammatory bowel disease, a painful and chronic intestinal disorder that affects an estimated 1% of Canadians. We have shown that greater numbers of gaps in this layer (i.e. missing cells) result in more problems in the gut. We have also discovered that these missing cells die through a special pathway called pyroptosis (fiery death). When the cells lining the intestine die from fiery death, they produce substances that activate the immune system and cause inflammation in the intestine. In addition, fiery cell death results in leaky holes in the intestine, allowing small particles and bacteria to enter into the body. This causes infection and further inflammation. Our objective is to outline the mechanism that leads to the fiery cell death and how all the factors fits together to cause inflammatory bowel disease. This is a new area of research: it was previously believed that the cells lining the intestine were killed as a result of the disease, instead of potentially being the source of the problem. Research into fiery cell death in the development of inflammatory bowel disease may lead to much improved therapies for patients with the disease.